New Protein Identified That May Contribute to Alzheimer’s Disease

Alzheimer’s Disease Dementia Brain Eraser Concept

Scientists from Brigham and Women’s Hospital identified a new protein that may contribute to Alzheimer’s disease.

Scientists at Brigham and Women’s Hospital identified a new protein, ganglioside GM2 activator (GM2A), that might contribute to the cause or progression of Alzheimer’s disease. Unlike the currently researched proteins, GM2A consistently reduces neuronal firing and causes a loss of neurite integrity, potentially explaining cognitive decline in Alzheimer’s patients.

Alzheimer’s disease (AD) is a debilitating progressive illness that begins with mild memory loss and slowly destroys cognitive function and memory. It currently has no cure and is predicted to affect over 100 million people worldwide by 2050. In the United States, AD is the leading cause of dementia in older adults and the 7th most common cause of death, according to the National Institute on Aging.

Ongoing Alzheimer’s research is focused on two key neurotoxic proteins: amyloid beta (Aβ) and tau. Although these proteins have been shown to be associated with AD, the levels of Aβ and tau do not consistently explain or correlate with the severity of cognitive decline for some people with the disease.

Investigators at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, set out to identify other proteins that may be directly involved with fundamental aspects of AD, like synaptic loss and neurodegeneration. They exposed laboratory neurons to human brain extracts from about 40 people who either had AD, were protected from AD despite having high Aβ and tau levels, or were protected from AD with little or no Aβ and tau in their brains.

The scientists identified and validated ganglioside GM2 activator (GM2A) as a protein able to reduce neuronal firing and induce a loss of neurite integrity. These protein characteristics may contribute to the cause of AD, progression of the disease, or both.

“Our data helps identify a new and potentially important protein that may be associated with the pathogenesis of Alzheimer’s disease,” said senior author Tracy Young-Pearse, PhD, from the Department of Neurology. “Interestingly, GM2A has been previously implicated as a causative agent in a lysosomal storage disorder very similar to Tay-Sachs disease, another condition like AD that destroys neurons.”

Reference: “Elevated ganglioside GM2 activator (GM2A) in human brain tissue reduces neurite integrity and spontaneous neuronal activity” by Yi-Chen Hsieh, Joseph Negri, Amy He, Richard V. Pearse II, Lei Liu, Duc M. Duong, Lori B. Chibnik, David A. Bennett, Nicholas T. Seyfried and Tracy L. Young-Pearse, 21 September 2022, Molecular Neurodegeneration.
DOI: 10.1186/s13024-022-00558-4

1 Comment on "New Protein Identified That May Contribute to Alzheimer’s Disease"

  1. How does this tie in to research from Stanford (2017?) and recent research in which the Brains ‘garbage collection process’ was disabled causing memory issues (maze navigation and decision making) and subsequently re-enabled with seemingly recovered abilities?
    Also in the more recent research (can’t find the article), the enable/disable agent was doxycycline.

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